The Transgenic and ES Cell Core of the JHU-UMD DRC will enable Members at Johns Hopkins University and the University of Maryland to efficiently generate transgenic and knock-out/in mice. Fredric E. Wondisford, M.D. will serve as Director, and Sally Radovick, M.D. will serve as Co-Director. Both are highly qualified to direct this core and their direct involvement in diabetes and diabetes-related research should further enhance transgenic/knock-out services to JHU-UMD investigators. The Center will utilize the existing Transgenic Core at Johns Hopkins University School of Medicine with the addition of dedicated technical support to expedite generation of mouse models for DRC Members and at a lesser cost. The DRC will continue to generate targeted ES cells using highly reliable and efficient protocols. The intellectual aspects associated with the generation of transgenic and knock-out/knock-in constructs and the reagents necessary for ES cells generation have proved to important for many investigators. By concentrating experience and expertise in this Core facility, the Core will markedly accelerate the progress of discovery for Center investigators. Transgenic services will be located in JHU space that is already allocated to the existing facility, and this facility has adequate equipment. ES cell services will be located in the connected CMSC building, adjacent to Dr. Wondisford's laboratories, in 500 sq. ft. of space. Drs. Wondisford and Radovick will assist in the design of targeting constructs. The Core will be managed by Dr. Sidhaye, who will oversee the introduction of constructs into ES cells, identifying ES clones that have undergone homologous recombination along with the respective investigator's laboratory and preparation of cells for injection into blastocysts. Facilitating transport of genetically altered mice from JHU to UMD has been part of the Core's function. Alternatively, budgeted into the Core'are short-term housing costs at JHU for mice made for UMD Members, if their study protocol requires imaging or metabolic studies.